Managing Non-malignant Hematological Disorders And Role Of HSCT
Dr Vikas Dua
Hello everybody. So friends, my name is Dr. Vikas Dua and I'm heading the department of Pediatric Hematology, Pediatric Oncology and Pediatric Bone Mero transplant at Fortis Memorial Research Institute Gurgaon. Been into Pediatric Hematology, Oncology, all of you must be knowing that a pediatric hematologist sees patients who are less than 18 years of age, who have got blood disorders, who have got cancers, we even see solid tumors and we do bone marrow transplants in case that is required. And friends that are task given to me is to talk on managing non-melignant hematological disorders. So when we send non-melignant disorders, that means we are leaving aside cancers and we are just going to discuss on the benign aspect of hematology, what a pediatric hematologist sees, a very basic about managing these benign hematological disorders and is there a role of hematopoietic stem cell transplant or you can call bone marrow transplant in these disorders? We are going to discuss on that part as well. As we speak on 27 March 2024, the common non-melignant or benign hematological disorders, which are pediatric hematologists sees in his practice are diseases like thalassemia, diseases like sickle serenemia and problems like a plastic anemia. I am not saying that we don't see nutritional anemia or other hematological disorder, but these are the non-melignant hematological disorders which are pediatric hematologists like me sees very often in his or her clinic and there is a definite role of bone marrow transplant for these three disorders and we will be discussing one by one these disorders. Let's understand the basics of thalassemia, very basic thing of thalassemia. So I don't know how many of us know the fact that India is the thalassemia capital world. Having said that, maximum number of thalassemics are born in India. I would say roughly 10,000 new birds are of thalassemia in a country like ours. Around 10,000 new thalassemics are added every year and that's why India is called thalassemia capital of the world. And what this problem is friends, it's a genetic disorder. It's an inherited blood disorder. You can call it a genetic disorder caused by a mutation, a genetic alteration because of that the patient requires blood transfusion from the age of six months. This simply means that the parents are carriers. You can call the parents as carriers as minors or as traits. And if two minors or two carriers get married, you can see in this cartoon, there is a 25 percent chance that they may produce a baby who has got thalassemia major. So what this thalassemia major is, these patients have got defective hemoglobin and from the age of six months, they start requiring blood transfusion. That means from the age of six months, these patients have to visit a clinic, have to visit a doctor, have to visit a hospital for blood transfusion. And if they don't do that, their hemoglobin drops and they may have big liver and a big spleen which is called hepatospemmically, they may have thalassemic faces. So we need to simply understand the fact that if two thalassemia minor or carriers get married, there is a 25 percent chance that they may produce a thalassemia major baby in each and every pregnancy. This doesn't mean that if in first pregnancy they got a thalassemia major baby, they will not have any thalassemia major baby in next three pregnancies. No, that is not the correct thing. This simply means that in each and every pregnancy, there is a 25 percent risk which these carriers have. In India, we always say that before marriage or at least before conception, the parents should do a simple blood test called HPLC and should know their thalassemia status. They should know whether they are carriers or not so that a birth of a thalassemia major baby can prevent it. Spending roughly 800 rupees for a test called HPLC is easy rather than managing a patient who has thalassemia major and who has been requiring blood transfusion or requires a one time cure which is called bone marrow transplant. So what we have just said, they are severely anemic in the first year of life usually at around six months and because of the low hemoglobin, they may be having fatigue, they may have liver disease, why liver disease because they require monthly blood transfusion. Every month these patients require blood transfusion and each and every unit of blood comes with elemental iron and this elemental iron gets deposited in the liver and in the heart and cause liver disease and heart disease. They may have abdominal pain and because of medicines called chelating agents, there are certain medicines which are called iron chelators which are given to these patients to decrease the iron level in the body and that can cause joint pain. One medicine is called kelfer and with that medicine there is a 30% chance that the patient may have joint pain and these patients may have joint pain because of the medicine or because of low hemoglobin, they may have joint pains. How to diagnose thalassemia major? We have discussed about that a simple blood test called CBC and a test called HPLC. High pressure liquid chromatography or a similar test called hemoglobin electrophoresis can be done to confirm the diagnosis but in some cases when you are not sure about the diagnosis and in case the patient has received blood transfusion before this blood test has been performed then you need to do a genetic test to know which type of mutation this patient has and that would help in confirming the diagnosis of thalassemia major. The treatment is simple because these patients have got low hemoglobin, they require blood transfusion from the age of 6 months and because each and every unit of blood comes with iron so to decrease the iron in the body they may require iron chelators and there are 3 iron chelators which are available in our country. One is called desferoxamine which is IV form intravenous form and 2 oral forms one defriperon and other one is called defriserox. So there are good and bads of all these iron chelators but these patients require iron chelation once their ferritin level when once their iron level exceeds more than 1000 in their blood. That's one way to treat. The other way or I would say the permanent cure for thalassemia is bone marrow transplant. The correct term or the new term is hematopoietic stem cell transplant which simply means that the patient's bone marrow is defective, is producing defective red cells and you are getting rid of that defective marrow by a healthy donor's marrow and that is called hematopoietic stem cell transplant and we always urge families who have kids suffering from thalassemia major to go for a transplant at the soonest because with as the age increases as the patient gets more blood transfusions there would be more iron in the body and more chance of complications so sooner the better. It is always advisable and it is better to get a transplant done early in their life. Another kind of I would say non-mellowing dominant disorder or a benign hematological disorder which we see in our practice is called sickle serenemia. Friends India is the thalassemia capital of the world which simply means maximum number of thalassemics are born in India. In a similar way Nigeria is the sickle cell capital of the world which means maximum number of sickle cell patients are born in Nigeria. We see a lot of patients who come to us from different parts of Africa for a permanent cure for sickle serenemia and that is transplant. Other than Nigeria, Uganda, Ghana, Tanzania, Zambia and some other African countries you see quite a number of sickle serenemia patients and in India there are certain belts like Chhattisgarh is the belt where you see maximum sickle cell in this country. Other than Chhattisgarh you may see sickle cell in some parts of Madhya Pradesh, you may see sickle cell in some parts of Gujarat, in some parts of Maharashtra. What the sickle cell is? It is another type of hemoglobinopathy like thalassemia in which the two parents are carriers like it was in the case of thalassemia but they carry a different mutation and they have been called sickle cell trade and if two trades, if two sickle carriers get married then there is a 25% chance that they may produce a sickle cell anemia baby. That means the red cell of these sickle cell anemia babies would be defective in shape, would be C-shaped, stiff, sticky, they have tendency to have a cluster formation and can block the blood vessels and their lifespan of these sickle shaped red cells is less is around 14 days as compared to the normal red cell lifespan which is 100 to 200 days, 100 to 120 days. So sickle cell disease patient have got two copies of defective genes whereas a carrier or a trade has got one copy. This we always tell that if two carriers are getting married there is a 25% chance that they may produce a sickle cell disease baby whereas in case there is one carrier and the other one is a sickle cell patient. If they get married there is a 50% chance that they may produce a sickle cell disease baby and 50% chance that they may produce a carrier or a sickle cell trade and in case both the parents are having sickle cell then there is 100% chance I would say 100% all the kids would be having sickle cell and in case there is one trade and other the other parent is normal then the family need not to be worried because there is a 50% chance that they may produce an unaffected baby and 50% chance that they may produce a trade who would just have the mutation but note would not be symptomatic. So the most severe form which is called sickles or anemia or you can call it HBSS is the most common and the most severe form they may have severe or chronic anemia and they may have other symptoms which we will be discussing in next few slides. There may be a variety which is called HBSC disease there may be a variety which is called HBS beta thal trade in which the manifestations are slightly different from sickle cell. So what symptoms do these patients have? So friends these patients who have got sickles or anemia they may come to a hematologist or pediatric hematologist with low hemoglobin. The usual presentation of these patients is pain crisis. If you remember what we discussed in the previous slides these red cells are defective, are C-shaped and they can block the blood vessels. Blocking of the blood vessels means the blood flow to the tissues would be less and they may have pain crisis, they may have swollen hands and feet and they can come to a doctor a care provider with painful crisis. If the blood vessels in the lungs in the lung vasculature is affected they may come to a doctor with a presentation like fast breathing fever which is called acute chest syndrome. These patients who have got sickle cell are friends also at risk of high, they are also at risk of infections mainly bacterial infections that's why prophylaxis, pencil in like medicines are being advised to these patients. Other than this they may have big spleen, they may have an issue called stroke. If a vessel in the brain is being clocked by a sickle cell these patients may have stroke, stroke means there may be a defective half side of the body or both side of the body may not be functioning well and because of the breakdown of these red cells defective red cells because red cells break early in sickle cell these patients may have indirect hyperbylruginemia or jaundice. The simpler way to diagnose these babies is by a complete hemogram or a CDC the way we do for thalassemia and another test which we do for thalassemia which is called HB electrophoresis high pressure liquid chromatography or hemoglobin electrophoresis can diagnose sickle cell anemia as well and in case this is the doubt then you can do a genetic test you can do a next generation sequencing and come to know which mutation which genetic alteration is responsible for causing sickle cell in that patient. Coming to the treatment strategies so friends as these patients are at risk of infections mainly bacterial infections or you can call it sepsis these patients are put on prophylactic anti-bacterial like pencilins these patients require vaccinations these patients are at risk of encapsulated infections you can like pneumocal etchin flinze meningocal baby cia that's why it's important to vaccinate these patients with these vaccines it is important for them to go to the healthcare provider in case they have any feature of infection like fever the medicines which is required for these patients are quite a number of the most common medicine which is been approved by FDA is called hydroxaurea hydroxaurea is a medicine which is given orally to sickle their anemia patients and it would increase the HBA level and would decrease the complications decrease the HBS level and would decrease the chances of pain crisis would decrease the chances of stroke would decrease the chances of chest syndromes and quite a number of complications which can happen because of sickle cell can be the chance of that can be decreased with hydroxaurea but friends newer medicines are been approved by FDA but somehow that is not available in India have been approved recently and can also be given to these patients to decrease the chance of complications in case the hemoglobin drops less than seven or eight then these patients may require blood transfusion as well if these patients are requiring chronic blood transfusion if these patients are behaving like a thalassemia patient and requiring chronic trans and may need a hospital and may need IV fluids to maintain the hydration and may need stronger painkillers like opioids the commonest opioid which all of us know of is morphine in the in case of acute chest syndrome the prophylaxis remains hydroxaurea but for the treatment antibiotics are been given and transfusion in case the hemoglobin is low in case of sphylinck sequestration the hemoglobin drops further lower down and these patients require blood transfusion and similar is the case for stroke you need to dilute the HBS and you need blood transfusion in cases of stroke as well as we speak on today's date the all knee permanent cure for sickle cell anemia is a bone marrow transplant you need to counsel these families of the need of a transplant we will be discussing who can be the best donor how we do a transplant in next subsequent presentation but we need to understand the fact that bone marrow transplant is the permanent cure there are studies studies which are going on gene therapy in the west but as we speak on today's date the permanent cure remains bone marrow transplant there may be that may be replaced by gene therapy in future we don't know but at present transplant is the all knee permanent cure for sickle cell so that was about thalassemia and sickle cell which are the two hemoglobin of a thies let's come to another very important important non-melignant or a benign disorder which we ask pediatric him at all to see and it's called aplastic anemia what is aplastic anemia friends the red cells white cells and plate rates are being formed from the bone marrow we have all got long bones inside the long bones you have got a spongy thing which is called bone marrow and red cells white cells and plate rates are being produced from the bone marrow in case of aplastic anemia the bone marrow is defective and the number of red cells white cells and plate rates which have been produced from the marrow goes down that means as the hemoglobin drops the patient would be feeling weak fatigue tired as the neutrophils or white cells drop these are the important cells which fight against infection so these patients would be at risk of infection and because the platelets drop there would be increase risk of bleeding or bruising in these patients what are the causes the causes can be you can divide that into two parts one is you can say non-genetic and second one is genetic so when we say non-genetic that is acquired they may have a empty marrow so infections like viral infection can cause aplastic anemia they may have a history of drug intake some drugs can cause aplastic anemia if these patients have a history of radiation so radiation is another culprit which can cause aplastic anemia but friends there could be idiopathic thing you may not be knowing the cause that can also happen that a patient has got a defective marrow is not able to reduce red cells white cells and plate rates but doesn't have a predisposing reason doesn't have history of viral infection doesn't have a history of drug intake doesn't have a history of exposure to radiation so idiopathic can be another cause for aplastic anemia but friends there could be some genetic causes these are called inherited bone marrow failure syndromes so there could be some genetic causes because of it you can have aplastic anemia and these genetic causes are like frankenizanemia that's the most common inherited bone marrow failure syndrome they can have dyskeratosis, kajanata they can have a swatchman diamond anemia they may have amaecal mastatic thrombocytopenia and last but not the least diamond blackened anemia so these are the five genetic causes for aplastic anemia or you can call them as inherited bone marrow failure syndromes depending upon the similarity how we diagnose aplastic anemia we need to do a test called bone marrow test you need to do a bone marrow aspiration and you need to take out a piece of bone marrow to look at the solidarity if the bone marrow solidarity means how the bone marrow is functioning is less than 25% in case the bone marrow is less than 25% then you call it as seaway plastic anemia in case the marrow is functioning more than 25% you call it non-seaway plastic anemia why this is important because those patients who have got non-seaway plastic anemia you can wait and the marrow can recover but somebody who has got seaway plastic anemia that means the marrow similarity is less than 25% then you have to treat how we treat that we'll discuss and there is another entity called very seaway plastic anemia that means the bone marrow similarity is less than 25% like seaway plastic anemia but the neutrophilic percentage the absolute neutrophilic count i'm pretty sure the doctors who would be seeing this presentation and would be listening to this presentation would understand those who have got an absolute neutrophilic count less than 200 along with a bone marrow similarity of less than 25% they are called patients they are the patients who have got very seaway plastic and how these patients present because of low hemoglobin they may have weak they may feel weak fatigue tired because of the low neutrophilic count they may have infections they may have fever because of low platelets they may bleed they may have bruce over the body if they have a history of a viral infection they may have jaundice you can call it hepatitis spleenomegalyaniniprotopetti it's wrongly mentioned it is not seen in a plastic anemia somebody who has got a plastic anemia doesn't have a spleen or a liver diagnostic thing we've already discussed the first thing is to do a complete bed count and the bone marrow aspiration and a biopsy is to be done to confirm the diagnosis of eight plastic anemia and to classify whether it is a severe or non-severein plastic so this is another condition which is i would say needs a urgent intervention or an intervention in the form of a transplant i give you an example let's say a patient has got a plastic anemia if i have to give an example let's say the car engine is not functioning so what is the best way to treat that what is the best way to i would say rectify that you change the engine of the car so that's called bone marrow transplant in case because of some reason you're not able to do a transplant then you can what you can do is you can try to rectify that engine you can try to polish that engine so that the car starts working well and that's called immunosuppressive therapy because these cells are the culprit cells which destroy the bone marrow so you can give a drug called anti-imoside globulin with another immunosuppressive medicine called cyclosporin and that can work in the norm 60-70 percent patients so friends all of us need to understand the fact that if you do a transplant then there's a 90 chance of a cure in a plastic anemia whereas if you give immunosuppressive medicine like ATG with cyclosporin rectify you can cure 60-70 percent patients so better is to do a transplant coming to internal about hematopoietic stem cell transplant as a treatment option for non-malignant disorders what is a transplant what is hematopoietic stem cell transplant it has been defined as intravenous infusion of autologous allleugenic stem cells to correct the defect in the marrow so simply means the bone marrow either you collect the stem cells from patient's body which is called autologous transplant or you collect it from a donor that is called allogeric transplant why because you want to re-establish the hematopoietic function which is happening in the like in thalassemia you have got a defective red cells in sickle you have got a defective red cells in a plastic the whole bone marrow is defective so you need a healthy donor's marrow to rectify these problems the first successful transplant friends was performed long back in 1959 by somebody called Dr. Daniel Thomas Dr. Daniel Thomas was the first person to perform successful transplant for a patient of leukemia a malignant disorder in 1959 and the same person performed the first successful transplant for a benign disorder which is called thalassemia in 1981. Friends more than 50 to 60 thousand transplants are being performed throughout the world i would say worldwide 50 to 60 thousand transplant are being performed and the outcome are being increasing day by day and the number of transplants are also increasing day by day two types you have already discussed auto and aloe autologous means your own stem cells are required for transplant allogeric means you require a donor you will come to the indications later but who is the best donor in case of allogeric transplant those who require allogeric transplant the best donor is a brother or a sister and that is called mat sibling donor transplant we need to do a test called hla typing because there is 25 to 30 percent chance that the patient would be full match to the donor on hla i'll give you an example let's say 100 patients require transplant and these 100 patients have got siblings 25 to 30 would be lucky enough to have a full match donor in the family that means they can go ahead and get a mat sibling donor transplant in case you don't have a full match donor in the family or you have the only child then you can put that hla report into a worldwide registry search and you make it a donor from outside friends the biggest registry in the world is called dkms that's in Germany second biggest registry is in us called nmdp we in india also have got one own registry which is called darthri which is in southern part of india so how does this registry works let's say i am the transplant physician i have a patient of thalamus in nia who is five-year-old requires a transplant and someone doesn't have a full match done in the family we have done the hla typing with the patient of the siblings or this is the only child and we don't have a full match in the family we put that hla report into a worldwide search and we can come to know whether somewhere somebody is matching with the patient or not because these registries they conduct camps in school colleges do the hla typing put that into their database and if somebody requires a donor he or she can send that hla report to the registry and the registry can tell you whether they have got a full match donor for your patient or not the donor doesn't have to fly the stem cells are being collected on a on a particular date which has been fixed after the discussion with the transplant physician with the family and the registry and stem cells are being shipped and you can do the transplant so friends that is matched unrelated donor transplant in a similar way you can do a quad blood transplant you can do a sibling quad blood transplant or you can do unrelated quad blood transplant when a newborn baby is born from from the placental side from the placental side you can collect the stem cells and you can use use that at a later date to do a transplant and that can be cryo-preserved in liquid nitrogen at minus 196 degree centigrade and that is called quad blood transplant but friends new grid on the block is called a half match transplant or a half-low identical transplant that means you can take parents as a donor you can do a half match transplant by taking parents as a donor because 50% of every child's gene comes from father and 50% of the genes comes from mother so parents are not fully matching with the patient but if you don't have the option of a full match donor in the family or outside the family you can take father or mother as a donor and you can do a half-mass transplant or a technical name for that is haplo identical transplant please understand the fact best donor is a full-match donor ad sibling donor then unrelated donor quad blood or a half-mass transplant haplo identical transplant can be done so in general if you ask me the indications of doing autoclose i would say conditions like malignant conditions like relapse, Hodgkin's lymphoma, relapse, non-Hodgkin's lymphoma, certain solid tumors like neuroblastoma, relapse, evening sarcoma and you can do autologous transplant from brain tumors like medalloblastoma and automendous autosalate like sce. so if you ask me what is the logic of doing a transplant, a hematopoietic transplant for solid tumors like neuroblastoma and medalloblastoma i would say that those patients who have got high risk neuroblastoma, high risk medalloblastoma that means that disease is aggressive it's not very sensitive to chemotherapy you want to give them heavy dose of chemotherapy but the flip side of that heavy dose of chemotherapy is that it is going to suppress the bone marrow so you collect the patient stem cells, blast the patient with the heavy dose of chemotherapy which is going to kill their cancer cells but the flip of that heavy dose of chemotherapy is that it's going to suppress the bone marrow of the patient so you give his or her own stem cells back so that is the logic of doing a autologous transplant in condition like evening sarcoma, neuroblastoma and medalloblastoma. coming to allogenic transplant, we as transplant physicians do allogen transplant for malignant disorders like AML, acute myeloid leukemia for high risk ALLs, for relapse, refractory AMLs, ALLs, we don't see CML much in our practice but we do see rarely CML happening in pediatric review it's a disease of adult age but those patients who don't respond to imatinamed may require a transplant for a condition called JMML, juvenile myeloid monosutative leukemia the only cure is bone marrow transplant and then another rare problem in in pediatric age group commonly seen in older age is MDS so MDS patients also require stem cell transplant or bone marrow transplant coming to the non malignant conditions nowadays we are doing transplants for non-hematological condition i would say like idunolegodistrophe, mucopolysaccharidosis like herulus disease, hunters disease, metachromatic leukodistrophe, osteopitrosis so these are certain non malignant non-hematological conditions which can be corrected with allogenic transplant genetic problems like primary neurodeficiencies, severe combined immunodeficiency, scency, viscous, address syndrome there are more than 300 primary neurodeficiencies which are known and many of them can be rectified with bone marrow transplant coming to BIL-9 hematological disorders we have discussed the rule of transplant and thalassemia for sickle cell for severe aplastic anemia for inherited bone marrow failure symptoms like panthenes anemia and for conditions like pure red cell dysplasia or you can call it diamond lactan anemia. The first and the foremost thing is to do hla typing and in case you have full-matched donor you would prefer that other options we have already discussed like mutt, match unerated donor transplant, quadratic transplant and glass but not the least a haplodentical transplant. These stem cells can be collected from the bone marrow the donor goes to the operation theta you can collect the stem cells from the bone marrow the donor goes to operation theta doctor collects the stem cells from the posterior superior lickspine and there's one nurse who is recording how much stem cells are been collected. Easier way is by collecting the stem cells from blood the donor gets some injections under the skin called granulocyte called dysprenidic factors which would mobilize the stem cells from the bone marrow to the peripheral blood and you can collect the stem cells in the blood bank no sedation is required no breaking of the bones easier way or when the new one baby is born from the quad blood the stem cells can be collected bone marrow is a very old source when people started doing transplants they just knew that bone marrow is the only source and they have the oldest experience with bone marrow but in recent times the majority of the transplant physicians are preferring collecting the stem cells from the peripheral blood rather than bone marrow though there are goods and bats of bone marrow and peripheral blood collection so we are not going to much of the details of that but to tell you peripheral blood is easier way of collecting you don't have to go to the operation theta the donor is not given any sedation the hematopotic recovery is faster if you do a peripheral stem cell transplant the stem cells recover faster as come to bone marrow the cost is less and are being a preferred source in majority of pediatric transplants is what I feel there are goods and bats of doing unlikely quad blood transplants I am not into too much of quad blood transplants because I feel that there are quite number of flips one flip is that because these are knife cells it may take a very long time to recover it may take four to six weeks to recover so there would be a higher neutroponic phase a long woman neutroponic phase more transverse infection but the good thing of quad blood transplant if I have to tell you is that as these are knife cells the chances of acute and chronic graft versus root disease would be less at this point we have already discussed 25 to 30 percent people would be lucky enough to have a fully matched donor in the family but for the rest 75 to 75 percent patients either you have to do unrelated donor transplant or a un-related quad blood transplant or a half-matched transplant like haploid integral transplant when we say under-grid registry the registry is because registry is DKMS then NMDP there is 80 chance that a Caucasian may get a donor from a registry whereas for a patient of Asian registry Asian origin the chance of finding a donor is less because of the under-representation of the donors from Asia in these registries how we do a transplant when we when we when we say that this patient is a is qualified for transplants let's say a thalasse in a five-degree example again a five-year-old thalassemic who requires a transplant we have done the HLA typing you come to know that they have got a full-matched donor then you admit the patient the patient is being admitted to the credit you do some battery of blood test to be sure that the patient is clean to accept the stem cells and the donor is clean to accept to donate you admit the patient patient gets a line a central line like a Hickman catheter or a peripheral inserted central catheter is given some chemotherapy called conditioning you can call it myelobulated conditioning or a reconditioning depending upon the underlying indication to empty the marrow to create a space to decrease the chance of rejection small therapy is given from six to ten days depending upon the underlying condition then four days before the transplant you start donors injection which is called GCSA and on the day of infusion in the morning you put a neckline or a femoral line to the donor and you collect the stem cells if it's a peripheral collection in the blood bag if it's a bone marrow collection then no need to give GCSA the donor goes to operation theta and you collect the stem cells on the bone marrow you infuse the stem cells on the day of infusion which is called day zero then there's a neutrophilic phase that means the counts would be low the hemoglobin would be low by itself would be low platelet should be low because of the effect of the conditioning and usually after two weeks the stem cells the donor stem cells start functioning and that is called neoprophilic engraftment which happens after two weeks in a peripheral transplant and usually after three weeks in a bone marrow transplant and once this happened you say that the neutrophils have engrafted and later plateletin graft and red cell engraft in the post engraftment period the patient may face problems like blood versus source disease may have issues of rejections and may have viral reactivations and bacterial infections so just what i have discussed just to tell you again conditioning period is seven to ten days and you have to create a marrow space so that you can the donor cells can be accepted some in some disorders radiation can also be used as a part of conditioning you may require myeloblytic conditioning a non-myeloblytic conditioning or reduced toxicity conditioning depending upon the underlying condition and there are goods and bats of myeloblytic and are reconditioning so they're not going to go into detail and these are different types of conditioning which people have used combination of glutar bine with radiation combination of cyclophosphamide with radiation combination of chemotherapy agents like duke-ducelphin cyclophosphamide which we use pathalassemia thiotipatrioselphin glutar bine which we use pathalassemia blue-blue is a very common well-known conditioning which we use for our amyl patients and there are coke some other conditioning regimens also stem cell infusion is not difficult it's like a blood transusion it's at 20 minutes to 30 minute process and it's done in a in a sterile procedure the sterile sterile room like a hyperfilted room in the BMT unit and stem cells once are collected can be infused freshly or in case of a haploid at integrated transplant you can do stem cell manipulation you can deplete the T cells which is called T cell depletion or you can do a T cell TCR alpha beta depletion to deplete the bad cells which cause GVHD and you can infuse the restaurant product which has got dendritic cells, NK cells and stem cells as well to decrease the chances of graft versus host disease the target stem cell dose is what we we want is two into 10 to the power six stem cells per kg of the respite weight or you can say two into 10 to the power eight nucleated cells per kg of the respite's weight stem cells manipulation may be required of the blood group incompatibility like in major incompatibility or or bidirectional incompatibility in case of haploid integral transplants we have discussed you may have to do a T cell depletion or you can even do a T cell depletion transplant in a haploid setting and you give a drug called cycloposphide on day three day four post transplant which would attack the alloreactive T cells and decrease the chances of complications these are the stem cell collection bar in which we keep the stem cells and in case you are thinking of doing the transplant later and you are preserving them these stem cells you can use a preservative like DMSO. Neotropinic phase is the phase which is there after transplant and at that time you are at a risk of bacteria and fungal infections after the engraftment happens the patient is at risk of engraftment syndrome can have viral reactivations after that the most transplant period it is very important to these manage these patients because these patients will be well well controlled range you'll be winning off immunosuppressive agents there is a bleak chance of chronic GVHD and you have to document immune reconstitution after the transplant complications like GVHD which is the most common complication graft versus those disease that means the patients stem cells donor stem cells are infused in the patient's body i'm saying these are not my body and start attacking they can have they can attack the skin they can attack the gut they can attack the liver so the patient may have got may have skin rash may have loose motions vomiting may have john this if it happens within 100 days of transplant it's called a cute GVHD if it happens after 100 days it is called chronic GVHD and depending upon the type of transplant what you're doing the chances are variable like in a bad sibling transplant the chances are least whereas in a haplo transplant T cell completed haplo transplant the chances are more a cute GVHD or what i would say what are the risk factors if the more actually incompatibility more than the chance of GVHD more gender if there's a gender mismatch female donor male recipient more chance of GVHD if you are increasing the dose of TBI high dose of TBI more chance of GVHD in case you have reduced the dose of methotrexate after transplant by around 80 percent then more chance of GVHD if the recipient age is more more chance of GVHD and in case of peripheral blood transplant chance of GVHD is more as compared to bone marrow symptoms we have already discussed treatment is immunosuppressivation the first line therapy is steroids but ATG psychosporin mycophanoid mephotel and certain other newer medicines can be used to create a cute GVHD for the for the chronic GVHD also more incompatibility more chance of GVHD if there's a history of prior acute GVHD more chance of chronic GVHD advanced recipient age in case of peripheral blood as a stem cell source more chance of chronic GVHD in case you have not used prophylactic medicines well then these patients are at high risk of GVHD and chronic GVHD can affect mouth you can have dry mouth you can have dry skin you may have dislrofit nails you may have hair loss you may have lung issues broncholitis obstetricans you may have decreased appetite nausea vomiting diarrhea you may have joint stiffness muscle weakness you may have vaginal dryness in case of females you may have I would say scarring in the urethra narrowing of the urethra in case of males and the first line therapy for chronic GVHD is also steroids but other medicines are being approved for GVHD as well other complications have very such slight as VOD organ toxality pulmonary syndrome and last few slides about the ATG so ATG as a conditioning regimen is being used to decrease the chances of GVHD acute and chronic GVHD well known and also to reduce the risk of least late mortality and it has helped in improving the quality of life because if the rates of GVHD goes down the outcomes are better we all are familiar with GVHD and studies EPMT study other studies have shown less chances of acute and chronic GVHD with the use of ATG with that I would like to thank you all for a patient hearing and please do please feel free to share your questions and I'll be happy to answer those thank you very much. I am out and I am nice to have this profit with you may have hair loss.
